The National Institute for Health and Clinical Excellence (NICE)
has released a positive Final Appraisal Document (FAD) in support of the use of Mimpara®
(cinacalcet) for the treatment of severe secondary hyperparathyroidism (SHPT), a serious
complication of kidney failure, in patients with end stage renal disease (ESRD) on
maintenance dialysis therapy.

SHPT is a common complication of ESRD, where the parathyroid hormone (PTH), which
controls calcium and phosphorus metabolism, is over-produced. Although SHPT can start
without any symptoms, it can slowly cause significant damage to the bones, heart and blood
vessels and if left untreated is associated with an increased risk of hospitalisation, surgery
and mortality.1-5 The number of patients on dialysis in the UK is around 18,400 with up to a
third of these patients affected by SHPT that has not responded to traditional therapies.6

Dr Richard Fluck, Consultant Renal Physician, Derby Hospitals Foundation NHS Trust
commented, “SHPT can be a debilitating condition for people with end stage renal failure,
with existing therapies often unsuccessful in treating this condition effectively. The advent of
cinacalcet has helped to increase SHPT treatment options for patients and as a result,
today’s NICE announcement is likely to be welcomed by all those affected by this condition.”

Cinacalcet works on the parathyroid gland, reducing the secretion of PTH and subsequently
lowering serum calcium and phosphorus levels in dialysis patients with SHPT.7 A published
study has shown that patients taking cinacalcet plus standard therapy are less likely to
experience bone fractures, cardiovascular hospitalisation, or surgery to remove their
parathyroid gland, than those taking placebo plus standard therapy.8

Tim Statham, Chief Executive of the National Kidney Federation, explained, “For many years
renal patients have searched for a solution to help them achieve better control of the mineral
balance in the body. They have needed a treatment that decreases their pain and improves
their quality of life. The treatment of a condition such as SHPT has been overlooked for too
long, until now.”

Treatment of kidney failure and its complications, including SHPT, was made an NHS priority
in 2001 by the National Service Framework (NSF) for renal services. The treatment of
clinically relevant hyperparathyroidism is also recommended in recent guidelines published
by the Royal College of Physicians on anaemia management in chronic kidney disease.9

“Amgen is delighted that the UK’s commitment to improving the treatment of kidney failure
has been further reinforced with today’s NICE announcement on cinacalcet,” explained Dr
Charles Brigden, Medical Director at Amgen.

Secondary Hyperparathyroidism (SHPT)

Secondary hyperparathyroidism (SHPT) is a complex complication of end stage renal disease,
involving abnormalities of parathyroid hormone (PTH), calcium, phosphorus and calcium-phosphorus
product. Factors in the development of SHPT are decreased production of calcitriol (the active form of
vitamin D) by the kidneys leading to hypocalcaemia (low calcium levels). Increased renal phosphorus
retention, leading to hyperphosphataemia, can also occur due to the kidneys’ inability to excrete it
effectively. This in turn leads to excess PTH secretion and eventually increased parathyroid gland
size.

End Stage Renal Disease (ESRD)

End stage renal disease is a complete or near complete failure of the kidneys to function. It usually
occurs as chronic renal failure worsens to the point where kidney function is less than 10% of normal.
At this point, the kidney function is so low that without dialysis or kidney transplantation, complications are multiple and severe, and death will occur from accumulation of fluids and waste products in the body.

About cinacalcet

In clinical trials in secondary HPT patients on dialysis, cinacalcet HCl was well-tolerated and effective
in reducing PTH, Ca, P, Ca x P in a broad range of patients regardless of age, gender, dialysis
method (hemo- or peritoneal dialysis), years on dialysis or disease severity.7

In a clinical trial in patients with hypercalcemia due to parathyroid carcinoma, cinacalcet HCl
significantly lowered calcium levels in the majority of patients.10

Studies have shown that cinacalcet HCl lowers Ca, based on its mechanism of action, so it should not
be initiated if a patient’s Ca levels are below the lower limit of the normal range.10 During dose titration,
Ca levels should be monitored frequently and if levels decrease below the normal range, appropriate
steps should be taken to increase Ca levels. The threshold for seizures may be lowered by reductions
in Ca levels and, infrequently, seizures have been reported. The most commonly reported side effects
are nausea and vomiting.10

About Amgen

Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer
since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing
safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have
changed the practice of medicine, helping millions of people around the world in the fight against
cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a broad and deep
pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically
improve people’s lives. To learn more about our pioneering science and our vital medicines, visit
amgen.

References:

1. Kim J et al, EDTA-ERA XLI Congress 2004; Abstract Book 12a, Abstract SO26.
2. Ganesh SK et al, J Am Soc Nephrol 2001 12 2131-2138.
3. Goodman WG et al, New Eng J Med 2000 342 1478-1482.
4. De Boer IH, Gorodetskaya I, Young B et al, J Am Soc Nephrol 2002 13 2762-9.

5. Block GA et al, J Am Soc Nephrol 2003 15 2208-2218.
6. UK Renal Registry, 8th Annual Report 2005 (renalreg).
7. Moe SM, Chertow GM, Coburn JW et al. Kidney International. 2005;67:760-71.
8. Cunningham J, Danse M, Olson K et al. Kidney International, 2005; 68:1793-1800.
9. Anaemia Management in Chronic Kidney Disease. National clinical guideline for management in
adults and children, 2006. p63, paragraph R17.
10. Mimpara® Summary of Product Characteristics.